Week 10: Diabetes Drugs

Type 1 vs Type 2 diabetes

• Type 1: body doesn’t make any insulin

• Type 2: insulin resistance — cells ignore insulin

What contributes to the development of T1 diabetes?

• Genetics

• Celiac

• Thyroid disease

Risk factors for T2 diabetes

• Males

• Older age

• Having a first-degree relative with it 

• BMI >25

• Sedentary lifestyle 

• CV disease (e.g., hypertension)

Hyperglycemia causes damage to _____ ______

blood vessels 

• both macrovascular and microvascular

What may occur d/t macrovascular complications r/t hyperglycemia?

• Peripheral vascular disease 

• MI 

• Stroke 

What may occur d/t microvascular complications r/t hyperglycemia?

• Diabetic nephropathy — renal insufficiency and failure 

• Diabetic retinopathy — blindness

DM diagnosis — A1C level

A1C ≥6.5%

DM diagnosis — fasting BG

FPG ≥126 mg/dL

DM diagnosis — 2-hour BG levels during oral glucose tolerance test (OGTT)

OGTT ≥200 mg/dL

DM diagnosis — Random BG and symptoms

Random BG ≥200 mg/dL 

AND

Classic symptoms of hyperglycemia (polydipsia, polyphasia, polyuria) or hyperglycemia crisis (DKA)

Diagnostic criteria for pre-diabetes — A1C

A1C 5.7-6.4%

Diagnostic criteria for pre-diabetes —fasting BG

FBG 100-125 mg/dL

• indicative of impaired fasting glucose

Diagnostic criteria for pre-diabetes — 2 hour BG during oral glucose tolerance test (OGTT)

140-199 mg/dL

• impaired glucose tolerance 

A1C goal for non-pregnant people with diabetes 

≤ 7%

To achieve an A1C of ≤ 7%, what FBG and postprandial glucose (60-90 min after meal) be? 

• FBG 80-130 mg/dL

• Postprandial glucose < 180 mg/dL

What factors contribute to a patient’s A1C goal be higher (>8%)?

• Older adults (7.5%, 8% for those with significant comorbidities)

• History of severe hypoglycemia 

• Advanced complications 

• Limited life expectancy 

• Little likelihood of benefit from intensive therapy

Hypoglycemia kills you _____, hyperglycemia kills you ____

• Hypoglycemia kills you quickly

• Hyperglycemia kills you slowly

Drugs to treat diabetes (8)

• Insulin

• Biguanides

• Sulfonylureas

• Thiazolindinediones (glitazones)

• Glinides (meglinides)

• DPP-4 inhibitors

• SGLT2

• Incretin (GLP-1) mimetics

Biguanide drug

Metformin (glucophage)

Sulfonylurea drug

Glipizide (glucotrol)

Thiazolindinedione name

Pioglitazone (actos)

Glinides name

Repaglinide (Prandin)

DPP-4 inhibitors name

Sitagliptin (Januvia)

SGLT2 name

Canagliflozin (invokana)

Incretin (GLP-1) mimetics names (2)

• Exenatide IByetta)

• Semaglutinide (Ozempic)

Diabetes drugs that can cause hypoglycemia (3)

• Insulin

• Sulfonylureas

• Glinides

Insulin

a hormone produced by the pancreas that regulates blood glucose by allowing it to enter cells for energy

Insulin MOA

Glucagon MOA

Goals of pharmacologic therapy

• Mimicking physiologic insulin production

• Typically includes a combination of basal & bolus insulin

• Goal is to effectively manage BG throughout the day & with meal

Basal Insulin 

• Long acting insulin

• Continuous insulin effects throughout day/night and between meals

Bolus (Prandial) Insulin

• Short acting

• Targets BG after meals and acts similarly to body’s natural insulin response to food

Prandial (Bolus) Insulin types

• Short-acting: Regular insulin (Humalin R)

• Rapid-acting: Insulin lispro (Humalog)

• Ultra-rapid acting: Insulin lispro (Lyumjev)

Basal Insulin types 

• Intermediate acting: NPH insulin 

• Long acting: Insulin glargine (Lantus)

• Ultra-long acting: Insulin glargine/Insulin glargine U300 (Toujeo)

What type of insulin is the only cloudy one?

Intermediate-acting: NPH insulin

What type of insulin cannot be mixed with another insulin?

Long-acting: Insulin glargine (Lantus)

Ultra-Rapid acting onset

1 minute

Ultra-Rapid acting peak (Lispro)

60-170 minutes

Ultra-Rapid acting duration (Lispro - Lyumjev)

4.5-7 hours

Ultra-Rapid acting uses (Lispro - Lyumjev)

• Multiple daily injection regimens

• Insulin pump

Rapid-acting onset (Lispro - Humalog)

within 15 minutes

Rapid-acting peak (Lispro - Humalog)

2 hours

Rapid-acting duration (Lispro - Humalog)

4-7 hours

Rapid acting uses (Lispro - Lyumjev)

• Multiple daily injection regimens 

• Insulin pump

Short acting onset (Regular insulin - Humalin R)

30 minutes 

Short acting peak (Regular insulin - Humalin R)

2-3 hours

Short acting duration (Regular insulin - Humalin R)

6 hours

Short acting uses (Lispro - Lyumjev)

• Multiple daily injection (MDI) regimens (SQ)

• Acute uses: DKA, Hyperkalemia (IV)

Intermediate acting peak (NPH - Humalin N)

6-12 hours

Intermediate acting duration (NPH - Humalin N)

12-18 hours

Intermediate acting duration (NPH - Humalin N)

• Multiple daily injection regimens

• often paired with rapid acting or regular insulin to improve mealtime coverage — immediate and longer-term insulin coverage

Long acting onset (Glargine - Lantus)

2-4 hours 

Long acting peak (Glargine - Lantus)

none

Long acting duration (Glargine - Lantus)

20-24 hours

Mixed insulin composition

• intermediate and rapid acting — Humalog mix

• 75% insulin lispro protamine and 25% insulin

Mixed insulin onset

15-30 minutes

Mixed insulin peak

1-6.5 hours 

Mixed insulin duration

10-16 hours

How is short-acting insulin effectiveness monitored?

post-prandial BG 

• 1-2 hours after starting a meal

How is long-acting insulin effectiveness monitored?

fasting BG

• no caloric intake for 8 hours

How do you mix NPH with short-acting insulin?

Nancy Regan RN

• Nancy = NPH — inject air into NPH vial 

• Regan = Regular insulin — inject air into regular insulin vial 

• R = Regular insulin —  pull out liquid 

• N = NPH — pull out insulin 

What angle should you administer insulin in a normal-sized person? Thin person?

• Normal: 45-90°

• Thin: 45-60°

When should clear insulin be discarded?

If it becomes cloudy

• except for NPH insulin — it is a cloudy solution 

Is insulin normally give SQ or IM? What is the exception?

• SQ

• Regular insulin always uses and IV

What types of insulin is preferred for pump therapy? (3)

Ultra-rapid, rapid, or regular

Premixed insulins are for ___ administration only, NOT for ___ or ___

• SQ

• pump or IV

What is the normal concentration of insulins?

100 units/mL

What temperature should insulin be stored in? What temperatures should be avoided? 

• Refrigerated temperature

• Do not put insulin in: 

  • NOT frozen — needs to be discarded if it freezes

  • Keep out of extreme heat!

How long can insulin be used after opening?

~30 days

Sliding scale insulin — 4 and 6 units

Give 4 units if BG is 150-200

Give 6 units is BG is 201-250

SQ injection locations (4)

• Abdomen 

• Thigh 

• Butt

• Upper arm 

Patient education for insulin administration

ensure patients can verbalize understanding of ther regimen and exhibit competency with insulin handling and injection

Hypoglycemia

BG < 70 mg/dL

How can someone prevent hypoglycemia/monitor it?

Monitor BG frequently

Risk factors for hypoglycemia in patients taking insulin

• NPO (typically pre- or post-surgery)

• Poor PO intake (N/V, diarrhea)

• Renal and liver diease

What are the 2 categories of hypoglycemia?

Neurogenic (level 1)

Neuroglycopenic (level 2)

What is neurogenic hypoglycemia and what are the symptoms? What is the BG below? 

Activation of the autonomic NS — BG <70 mg/dL

• starts with hunger and then follows with sympathetic nervous system symptoms:

  • anxiety

  • tachycardia

  • sweating

  • constriction of skin vessels (cool & clammy)

What is neurogenic hypoglycemia and what are the symptoms? What is the BG below? 

Altered cerebral function — BG < 54 mg/dL — REQUIRES IMMEDIATE INTERVENTION!!!

• symptoms:

  • Headache

  • problem-solving

  • confusion

  • altered behavior

  • coma

  • seizure

Hypogylcemia treatment: 15-15 rule

• 15 g fast-acting carbs 

  • Glucose tablets: 4

  • ½ cup of regular juice or soda

• Recheck BG 15 minutes after giving fast-acting carbs

Hypogylcemia treatment: Glucagon

given when patient is unconscious and is unable to eat or drink

Hypogylcemia treatment: D50

Given when patient is in the hospital/EMS d/t the severity of their hypoglycemia

Glucagon MOA 

Hormone secreted by the alpha cell in the pancreas

• Increases blood glucose level by stimulating glycogenolysis in the liver

• Immediately raises blood glucose level (5-20 min)

Lipodystrophy

a complication of insulin administration where there is abnormal loss or abnormal distribution of body fat d/t repeated insulin injections at the same site

• this will affect the absorption of insulin at that site

Biguanides prototype name

Metformin

Biguinides MOA

• Inhibits glucose production in liver

• Improves insulin sensitivity

  • sensitizes insulin receptors in target tissues

Biguanides (Metformin) is often the 1st line therapy for type-__ DM because of…

• 2

• Absorption, efficacy, and cost

Side effects of Biguanides (Metformin) (4)

• Does not cause hypoglycemia when used alone

• Decreased appetite, nausea, vomiting, diarrhea

• Decreases absorption of B 12 and folic acid

• Weight loss: ~7-8 pound

• Lactic acidosis

What substances can increase risk for Lactic Acidosis toxicity r/t Biguanides (Metformin)? 

• Alcohol

• Cimetidine (Tagamet),

• Iodinated radiocontrast media*

How long must Biguanides (Metformin) be held before and procedure with contrast?

48 hours

Thiazolidinediones (Glitazones) prototype

Pioglitazone 

Thiazolidinediones (Glitazones) MOA

Reduce glucose levels by decreasing insulin resistance and inhibit gluconeogenesis

How long does it take for Thiazolidinediones (Glitazones) to become effective?

2-3 months

Thiazolidinediones (Glitazones) adverse effects

• Weight gain

• Increased risk of HF and bone fractures d/t increased weight

  • Do not give this med to patients who are obsess/overweight

Sulfonylurea prototypes (2)

Glipizide XL

Glipizide Immediate release

Sulfonylurea (Glipizide XL and immediate release) Glinides (Repaglinide) MOA

• Glipizides: Stimulates pancreatic beta cells to increase insulin secretion

• Repaglinide: same as glipizides, but has rapid absorption and rapid elimination

Who cannot be given Sulfonylureas (Glipizide XL and immediate release) or Glinides (Meglitinides?

those whose pancreas cannot make insulin 

Sulfonylurea (Glipizide XL) onset

2-3 hours

Sulfonylurea (Glipizide XL) peak

6-12 hours

Sulfonylurea (Glipizide XL) duration

24 hours

Sulfonylurea (Glipizide immediate release) onset

30-60 minutes